Irisin is a novel myokine, secreted from skeletal muscle after exercise. Irisin mediates exercise-related energy expenditure by turning white adipose tissue (WAT) into brown adipose tissue (BAT). Thus, irisin is considered as a potential biomarker for obesity and metabolic syndrome. Infants born small for gestational age (SGA) have increased risk for metabolic syndrome. However, the physiologic role of irisin in neonates remains to be studied.To evaluate the association of umbilical cord blood irisin levels with gestational age and birth weight categories in neonates.A cross-sectional study of 341 newborns, from 26 to 41weeks’ gestation. We collected umbilical cord blood and analyzed plasma for irisin by ELISA.Plasma irisin levels were positively correlated with gestational age (r=0.21, p<0.001), and birth weight Z-score (r=0.18, p<0.001). SGA infants had significantly lower irisin (median [interquartile range] 55.38 [46.56–65.72]ng/mL) compared to appropriate for gestational age infants (64.41 [53.87–76.76]ng/mL) and large for gestational age infants (68.70 [54.78–79.09]ng/mL, p<0.01). The association between SGA and lower irisin remained significant in multivariate analysis independent of gestational age, maternal age, maternal BMI, and gestational diabetes (p=0.03). In singleton infants, irisin was also significantly negatively associated with maternal preeclampsia (p=0.01).Our results support the notion that irisin may have a physiologic role in neonates. We speculate that decreased levels of irisin in SGA infants may contribute to the development of catch-up growth and metabolic syndrome later in life.